Epitopes described in "The DBY gene codes for an HLA-DQ5-restricted human male-specific minor histocompatibility antigen involved in graft-versus-host disease."

Article Authors:Mario H J Vogt; Joost W van den Muijsenberg; Els Goulmy; Eric Spierings; Petra Kluck; Michel G Kester; Ronald A van Soest; Jan W Drijfhout; Roel Willemze; J H Frederik Falkenburg
Article Title:The DBY gene codes for an HLA-DQ5-restricted human male-specific minor histocompatibility antigen involved in graft-versus-host disease.
Reference Detail
Reference ID:1020294
Abstract:Graft rejection or graft-versus-host (GVH) disease after HLA-identical stem cell transplantation is the result of recognition of minor histocompatibility antigens (mHags) by immunocompetent T lymphocytes from recipient or donor origin, respectively. Cytolytic T lymphocyte (CTL) clones can be isolated during graft rejection and GVH disease to identify mHags and their corresponding genes. Thus far, all human mHags identified appeared to be HLA class I-restricted. Here, we report the characterization of the first human HLA class II-restricted sex-linked mHag involved in GVH disease. Previously, we isolated an HLA-DQ5-restricted CD4(+) CTL clone from a male patient with chronic myeloid leukemia who developed acute GVH disease grade III-IV after transplantation of HLA genotypically identical female stem cells. Using a panel of female HLA-DQ5(+) EBV cells that we stably transfected with Y chromosome-specific genes, we determined that the HLA class II male-specific mHag (H-Y) was encoded by the Y chromosome-specific gene DBY. The H-Y epitope was localized in the DBY protein using female HLA-DQ5(+) peripheral blood mononuclear cells loaded with DBY protein fragments. The minimal peptide sequence leading to maximal recognition by the specific HLA-DQ5-restricted CTL clone was characterized as the 12-amino acid sequence HIENFSDIDMGE. Although the epitope differed by 3 amino acids from its X-homolog DBX, only 2 polymorphisms were shown to be essential for recognition by the CTL clone.
Reference Type:Literature
PubMed ID:11929796
Journal Volume:99
Article Pages:3027-32
Journal ISSN:1528-0020
Article Chemical List:Epitopes;HLA-DQ Antigens;HLA-DQ5 antigen;Histocompatibility Antigens Class II;Minor Histocompatibility Antigens;Oligopeptides;Proteins;DDX3Y protein, human;DEAD-box RNA Helicases
Article MeSH List:Amino Acid Sequence; CD4-Positive T-Lymphocytes(immunology); DEAD-box RNA Helicases; Epitope Mapping; Epitopes(analysis; genetics; immunology); Female; Genetic Linkage; Graft vs Host Disease(immunology); HLA-DQ Antigens(immunology); Hematopoietic Stem Cell Transplantation(adverse effects); Histocompatibility Antigens Class II(genetics; immunology); Humans; Male; Minor Histocompatibility Antigens(genetics; immunology); Oligopeptides(chemical synthesis; immunology); Proteins(genetics; immunology); T-Lymphocytes, Cytotoxic(immunology); Y Chromosome
Curation Last Updated:2014-10-03 22:10:37